Biomedical subjects

P R Miles

Publications and source records attributed to P R Miles.

At least 19 recordsLinked to original sources

PubMed1999

Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages.

The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide (. NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. NO produced by the cells in response to LPS is due to an inducible. NO synthase (iNOS). Surfactant inhibits LPS-induced. NO formation in a concentration-dependent manner;. NO production is inhibited by approximately 50 and approximately 75% at surfactant levels of 100 and 200 microg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce. NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an approximately 80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced. NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits. NO formation in a concentration-dependent manner;. NO production is inhibited by approximately 50 and approximately 90% at SP-B levels of 1-2 and 10 microgram/ml, respectively. These results show that lung surfactant inhibits LPS-induced. NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.

Animals↗

PubMed1998

Constitutive nitric oxide production by rat alveolar macrophages.

Results from previous studies suggest that alveolar macrophages must be exposed to inflammatory stimuli to produce nitric oxide (.NO). In this study, we report that naive unstimulated rat alveolar macrophages do produce .NO and attempt to characterize this process. Western blot analysis demonstrates that the enzyme responsible is an endothelial nitric oxide synthase (eNOS). No brain or inducible NOS can be detected. The rate of .NO production is approximately 0.07 nmol.10(6) cells-1.h-1, an amount that is less than that produced by the eNOS found in alveolar type II or endothelial cells. Alveolar macrophage .NO formation is increased in the presence of extracellular L-arginine, incubation medium containing magnesium and no calcium, a calcium ionophore (A-23187), or methacholine. .NO production is inhibited by NG-nitro-L-arginine methyl ester (L-NAME) but not by NG-nitro-L-arginine, L-N5-(1-iminomethyl)ornithine hydrochloride, or aminoguanidine. Incubation with ATP, ADP, or histamine also inhibits .NO formation. Some of these properties are similar to and some are different from properties of eNOS in other cell types. Cellular .NO levels do not appear to be related to ATP or lactate content. Alveolar macrophage production of .NO can be increased approximately threefold in the presence of lung surfactant or its major component, dipalmitoyl phosphatidylcholine (DPPC). The DPPC-induced increase in .NO formation is time and concentration dependent, can be completely inhibited by L-NAME, and does not appear to be related to the degradation of DPPC by alveolar macrophages. These results demonstrate that unstimulated alveolar macrophages produce .NO via an eNOS and that lung surfactant increases .NO formation. This latter effect may be important in maintaining an anti-inflammatory state in vivo.

Adenosine Triphosphate↗

PubMed1997

Alveolar type II cell cNOS activity and ATP levels are increased by lung surfactant or DPPC vesicles.

In a previous study, we reported that nitric oxide (.NO) affects surfactant synthesis and ATP levels in alveolar type II cells and suggested that there is constitutive nitric oxide synthase (cNOS) activity in the cells. In the present study, we performed experiments to confirm further the presence of cNOS and to determine the effects of lung surfactant on type II cell .NO and ATP levels. The supernatant from freshly isolated cells contains .NO (0.26 +/- 0.08 nmol/10(6) cells). During incubation, the cells produce additional .NO at a rate of approximately 0.3 nmol.10(5) cells-1.h-1. .NO formation is inhibited by 28-46% by three inhibitors of cNOS and inducible NOS (iNOS), NG-monomethyl-L-arginine (L-NMMA), L-N5-(1-iminoethyl)ornithine hydrochloride, and NG-nitro-L-arginine methyl ester, but a specific inhibitor of iNOS, aminoguanidine, has no effect. The production of .NO is reduced in Ca(2+)-free medium, is stimulated by the Ca2+ ionophore A-23187, and is independent of extracellular L-arginine. One known type of cNOS, endothelial NOS (eNOS), can be detected in the cells by using Western blot analysis. Incubation of the cells with lung surfactant leads to a relatively rapid (approximately 15 min), concentration-dependent increase in .NO formation that reaches levels as high as 238 +/- 14% of control. The surfactant effects appear to be caused by its major component, dipalmitoyl phosphatidylcholine (DPPC). Exposure of type II cells to DPPC results in maximal increases in .NO formation, ATP content, and O2 consumption, which are 268 +/- 32, 234 +/- 24, and 131 +/- 6% of control, respectively. The DPPC-induced increases in .NO, ATP, and O2 consumption are inhibited by L-NMMA. These results confirm the presence of type II cell cNOS and suggest that it may have a role in the cellular processing of lung surfactant.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1996

Exposure to crystalline silica or treatment with chlorphentermine increases vitamin E levels in rat alveolar lavage materials.

Previous studies have shown that vitamin E may be an integral part of lung surfactant and may function to protect this material from oxidant damage. Therefore, we measured the vitamin E levels in alveolar lavage materials from rats exposed to crystalline silica or treated with chlorphentermine (CP), two treatments that are known to increase surfactant phospholipids (PL) by different mechanisms. Silica exposure leads to increased PL synthesis, and CP treatment causes a reduction in PL degradation. Two different silica preparations, HCL-washed and unwashed silica, were used because exposure to each of them leads to different degrees of phospholipidosis. Exposure to HCL-washed silica results in a more than 17-fold increase in lavage PL and protein levels and a 12.2-fold increase in the amount of vitamin E. Exposure to unwashed silica leads to an approximately 7-fold increase in PL and proteins and a 5.8-fold increase in lavage vitamin E. Following treatment of rats with CP, there is a 15- to 19-fold increase in lavage PL and proteins and a 13.6-fold increase in vitamin E. When the results are expressed as micrograms vitamin E per milligram of lavage PL or protein, there is not much difference between controls and each treatment group. Because surfactant synthesis occurs in the endoplasmic reticulum, we also measured vitamin E in lung microsomes. Both silica exposure and CP treatment also lead to 1.8- to 2.5-fold increases, respectively, in the lung microsomal levels of vitamin E. These results demonstrate that alveolar lavage vitamin E levels are elevated along with lavage PL and proteins, and lung microsomal vitamin E levels are increased following exposure of rats to silica or treatment of the animals with CP.

Animals↗

PubMed1996

Pulmonary microsomal metabolism of benzo[a]pyrene following exposure of rats to silica.

Because some evidence suggests that there may be an increased incidence of lung cancer in silicosis and because previous studies have shown that exposure of rats to silica alters the pulmonary cytochrome P-450 system, we studied the effects of exposing rats to silica on the lung microsomal metabolism of benzo[a]pyrene (BaP). Rats were exposed to silica by intratracheal administration, lung microsomes were obtained 2 wk later from untreated and silica-treated animals, and the amounts of microsomal tissue and metabolites formed during the in vitro microsomal metabolism of BaP were measured. When the formation of BaP metabolites in equal amounts of lung microsomal tissue from the 2 treatment groups is compared, 3-OH BaP, BaP 4,5-diol, and BaP 9,10-diol are reduced by 45-70%, but the formation of BaP 7,8-diol or the BaP-quinones is not significantly altered following exposure to silica. In fact, the ratio of the BaP diols and BaP quinones, potentially toxic metabolites, to the relatively nontoxic 3-OH BaP produced by equal amounts of lung microsomal tissue is increased more than threefold following exposure of rats to silica. Since exposure of rats to silica leads to increased levels of lung microsomal protein, the amounts of BaP metabolites that could be produced by all microsomal tissue in the lungs were calculated. In silica-treated animals, the calculated total lung production of 3-OH BaP, BaP 4,5-diol, and BaP 9,10-diol tends to be increased by 1.2- to 2.0-fold, but BaP 7,8-diol and the BaP quinones are increased by 3.5-fold. These results demonstrate that exposure of rats to silica may alter the capacity of the lungs to metabolize benzo[a]pyrene, and the greatest effect seems to be enhanced accumulation of BaP 7,8-diol and the BaP quinones.

Animals↗

PubMed1996

Nitric oxide alters metabolism in isolated alveolar type II cells.

Alveolar type II cells may be exposed to nitric oxide (.NO) from external sources, and these cells can also generate .NO. Therefore we studied the effects of altering .NO levels on various type II cell metabolic processes. Incubation of cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit this process. On the other hand, incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP content, and cellular oxygen consumption. The L-NAME effects are reversed by addition of L-arginine, the substrate for NOS. Production of .NO by type II cells is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than inducible NOS (iNOS), and is reduced in the absence of external calcium. Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content or on .NO production. These results indicate that alveolar type II cell lipid and energy metabolism can be affected by .NO and suggest that there may be cNOS activity in these cells.

Adenosine Triphosphate↗

PubMed1995

Properties of lavage material from excised lungs ventilated at different temperatures.

We studied the phospholipid (PL) and protein contents, the PL composition, and some of the surface properties of lavage materials obtained from freshly excised rat lungs and excised lungs which had been ventilated at different temperatures (22, 37, and 42 degrees C). Ventilation (60 breaths/min) was carried out at constant tidal volume with periodic sighs for one hour. Although there is slightly more lavageable PL and protein in lungs ventilated at 22 degrees C than in freshly excised lungs, there is no difference in the PL composition or surface properties of lavage materials from these lungs. However, as the temperature at which lungs are ventilated is increased to 37 degrees and 42 degrees C, there is(are): 1) a reduction in lavage fluid PL, 2) a reduction in the relative amounts of total phosphatidylcholines (PC) and disaturated PC (DSPC), the major surface active component of pulmonary surfactant, 3) an increase in unsaturated PC, and 4) increases in total protein and nonsedimentable protein (100,000 g; 2 hr) in the lavage materials. There are also differences in the surface properties of the lavage materials from lungs ventilated at higher temperatures when compared with freshly excised lungs or lungs ventilated at 22 degrees C, probably as a result of the changes in composition. Maximal surface tension is greater for lavage materials from lungs ventilated at 37 degrees C. For lungs ventilated at 42 degrees C, maximal and minimal surface tension values are increased. These results demonstrate that there are differences in the composition and surface properties of alveolar lavage materials from excised lungs ventilated at different temperatures.

Animals↗

PubMed1995

Particle activity and in vivo pulmonary response to freshly milled and aged alpha-quartz.

This study examined the possibility of freshly fractured alpha-quartz being more toxic and inflammatory in vivo than aged quartz of the same composition and particle size. Fresh quartz was generated by a jet mill, and used immediately, while aged dust was stored for two months before use. Both the production of hydrogen peroxide and hydroxyl radicals and the analysis of surface radicals verified the enhanced surface activity of fresh quartz. Male Fischer 344 rats were exposed to fresh or aged alpha-quartz by inhalation (20 mg center dot m-3, 5 h per day, 5 d per week, for 2 weeks) and their pulmonary responses were determined 1--3 d postexposure. Exposure to aged quartz resulted in an increase in cytotoxic and inflammatory parameters. In comparison, the inhalation of freshly cleaved quartz resulted in dramatically greater increases in all of the pulmonary responses. This finding suggests that exposure to freshly machined quartz may result in a greater risk of pulmonary disease.

Administration, Inhalation↗

PubMed1994

Changes in alveolar lavage materials and lung microsomal xenobiotic metabolism following exposures to HCl-washed or unwashed crystalline silica.

Intratracheal exposures of rats to crystalline silica washed with HCl to remove iron contaminants have previously been shown to increase lung surfactant phospholipids (PL) and proteins and to alter the pulmonary microsomal cytochrome P450 system. We compared these effects of HCl-washed silica with those produced by exposures to unwashed silica and alumina. Both silica preparations produce increases in lung weights and alveolar lavage PL and proteins, but to different degrees. The increases produced by HCl-washed vs unwashed silica are lung weights, 2.2- vs 1.3-fold; lavage PL, 25.9- vs 3.7-fold; and lavage proteins, 11.1- vs 3.2-fold, respectively. Although the two silica particles increase lung microsomal protein concentrations (expressed per gram lung) by 50-60%, their effects on cytochrome P-450-mediated xenobiotic metabolism are quite different. Exposure to HCl-washed silica leads to a 2.3-fold increase in 7-ethoxyresorufin O-deethylation, a reaction catalyzed by cytochrome P4501A1, and a 0.5- to 0.6-fold reduction in 7-ethoxycoumarin O-deethylation, a reaction which may be catalyzed by cytochrome P-4502B1. Unwashed silica does not alter the metabolism of either xenobiotic when results are expressed per milligram microsomal protein. Administration of alumina produces only minor increases in lung weight and lavage PL and no effect on microsomal xenobiotic metabolism. These results show that the increases in alveolar lavage PL and proteins induced by administration of unwashed silica are exaggerated by 3- to 7-fold if the silica is treated with HCl. Furthermore, exposure to HCl-washed silica results in significant alterations of the lung microsomal cytochrome P450 system, but the unwashed silica has little effect. Although the reason(s) for these different effects is not known, measurements of iron levels and formation of hydroxyl radicals using ESR demonstrate that there is more iron associated with the unwashed than with the HCl-washed silica.

Animals↗

PubMed1993

Alterations in alveolar type II cell metabolism induced by tetrandrine and other alkaloids.

Tetrandrine (TT) and other bisbenzylisoquinoline alkaloids have been used in China as a treatment for fibrotic lung diseases. Because of their potential use as pulmonary therapeutic agents, we studied the effects of some of these compounds on energy metabolism in isolated rat alveolar type II cells, i.e., cells which play a critical role in maintaining normal lung function. Incubation of type II cells with most of the alkaloids produces a reduction in cellular ATP content. However, there is no effect of the alkaloids on cellular oxygen consumption. All of the alkaloids which produce reductions in cell ATP levels cause increases in internal calcium levels of type II cells. Incubation of the cells with the calcium ionophore, 4-bromo A-23187, leads to increased amounts of intracellular calcium and reductions in ATP levels, but has no effect on oxygen consumption. Exposure of isolated lung mitochondria to calcium produces a concentration-dependent reduction in ATP synthesis with no effect on mitochondrial oxygen consumption. Direct exposure of mitochondria to TT has no effect on ATP synthesis. These results are consistent with the notion that the alkaloids produce an increase in type II cell internal calcium levels which, in turn, leads to reduced rates of mitochondrial ATP synthesis.

Adenosine Triphosphate↗

PubMed1993

Alterations in the pulmonary microsomal cytochrome P-450 system after exposure of rats to silica.

Because some evidence indicates that there is an increased incidence of lung cancer in silicosis, we studied the effects of exposing rats to silica on the pulmonary microsomal cytochrome P-450 system. Rats were exposed to silica by intratracheal administration, lung microsomes were obtained from untreated and silica-treated animals, and the amount of microsomal tissue, the level of total cytochromes P-450 (all isozymes), the activity of NADPH cytochrome P-450 reductase, the metabolism of two xenobiotics, and the relative amounts of cytochrome P-4502B1 and P-4501A1 were measured. Lungs from silica-treated rats were almost 2-fold heavier and contained more than 10 times more alveolar phospholipids than lungs from untreated animals, indicating that acute silicosis had been produced. In lungs from silica-treated animals, the concentration of microsomal tissue, expressed as milligrams of microsomal protein per gram of lung, was increased by more than 2-fold, and total microsomal protein content was increased by almost 5-fold relative to untreated animals. When expressed as activity or amount per milligram of protein, the microsomal concentrations of NADPH cytochrome P-450 reductase, total cytochromes P-450, 7-ethoxycoumarin (EC)-0-deethylase, and cytochrome P-4502B1 are reduced by approximately 50% in silica-treated rats. However, when expressed as total activity or amount in the lungs, all are increased by approximately 1.5- to 2.5-fold in silica-treated lungs. On the other hand, total lung 7-ethoxyresorufin (ER)-0-deethylase activity and cytochrome P-4501A1 are increased by 4- to 5-fold in silica-treated lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Alterations of pulmonary benzo[a]pyrene metabolism by reactive oxygen metabolites.

Superoxide anion radical and hydrogen peroxide (H2O2) are reactive oxygen metabolites which are thought to be involved in oxidant-induced lung injuries. Therefore, we studied their effects on the pulmonary metabolism of benzo[a]pyrene (BP) in rat lung microsomes. The microsomes were incubated with xanthine and xanthine oxidase to generate superoxide anion (effects verified with superoxide dismutase) or H2O2 and then the products formed during the metabolism of BP were measured. Both oxygen metabolites inhibit BP hydroxylase activity, i.e., the production of 3- and 9-hydroxybenzo[a]pyrene (phenols) in a concentration-dependent manner. The phenols account for approximately 75% of metabolite formation and are the major products of BP metabolism. Two components of the monooxygenase system responsible for BP metabolism, cytochrome P-450 and NADPH-cytochrome P-450 reductase, are also inhibited by the two oxygen metabolites in a similar manner. Superoxide anion is more effective than H2O2 in the inhibition of both BP hydroxylase and the monooxygenase components. Neither oxygen metabolite has any effect on the formation of minor metabolites of benzo[a]pyrene, i.e., BP-quinones and BP-dihydrodiols. These are the BP metabolites thought to produce toxic effects and which may lead to the formation of carcinogens and/or mutagens. The results of all these experiments suggest that exposure of lung microsomes to oxygen metabolites can lead to a slowing of overall BP metabolism and the increased accumulation of potentially toxic BP metabolites.

Animals↗

PubMed1990

Metabolic changes in alveolar type II cells after exposure to hydrogen peroxide.

Since oxygen metabolites may play an important role in pulmonary oxidant injury, the effects of hydrogen peroxide (H2O2) on energy metabolism in alveolar type II cells isolated from rats were studied. The major effect of H2O2 is a rapid and dramatic reduction in the steady-state level of cellular ATP; e.g., ATP levels are reduced by 77 +/- 3% after only 5 min of exposure to H2O2 (0.5 mM). Cellular oxygen consumption is affected in a similar manner, suggesting that ATP synthesis is impaired. Experiments with isolated lung mitochondria demonstrate that exposure to 0.5 mM H2O2 for 5 min inhibits the rate of mitochondrial ATP synthesis by 51 +/- 3%. The site of mitochondrial ATP synthesis inhibition by H2O2 appears to be the adenosinetriphosphatase-synthase enzyme complex which phosphorylates ADP to ATP. Mitochondrial electron transport is unaffected. The association of 3-O-methylglucose with type II cells and glycolytic metabolism, measured as lactate production, are reduced by 25-35% by H2O2. The data also show that the cells are capable of recovery following exposure to H2O2, at least at lower exposure levels. These results indicate that exposure of type II cells to H2O2 alters the energy state of the cells by decreasing ATP synthesis. In turn, other important cellular functions may be impaired.

3-O-Methylglucose↗

PubMed1990

Cytomegalovirus in the bronchoalveolar lavage fluid of patients with AIDS.

This study investigated the significance of detecting cytomegalovirus in the bronchoalveolar lavage fluid of patients with human immunodeficiency virus infection. Bronchoscopy with BAL was performed on all patients. Lavage was examined for CMV by cytology, culture, and immunofluorescence. The lavage results were compared to clinical status at the time of bronchoscopy and the outcome of the respiratory event. Cytomegalovirus was detected in 51 percent of the BALs in the patients with HIV infection and 25 percent of the immunosuppressed patients without HIV. No association was found in the HIV infected patients between CMV and hypoxemia, abnormal chest roentgenogram, leukopenia, and increased mortality. As indicated by mortality, CMV did not significantly increase the severity of Pneumocystis carinii pneumonia. The study also suggested that CMV in BAL fluid reflected bronchopulmonary replication of the virus, and not contamination by virus in the blood. Cytomegalovirus does not appear to contribute directly to the pulmonary disease found in most patients with HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Carbon tetrachloride inhibits synthesis of pulmonary surfactant disaturated phosphatidylcholines and ATP production in alveolar type II cells.

Other studies have shown that inhalation of carbon tetrachloride (CCl4) decreases the amount of pulmonary surfactant lining the alveolar surface. Therefore, we studied the effects of CCl4 on the synthesis of surfactant phosphatidylcholines (PCs) in rat alveolar type II cells in vitro. The rate of incorporation of choline, palmitate or glycerol into disaturated PC (DSPC) is decreased in a concentration-dependent manner. The CCl4 concentrations which cause maximal inhibition and 50% inhibition are similar for each substrate. The rate of incorporation of choline or glycerol into total PC is diminished to the same extent as their incorporation into DSPC. In addition, the rate of incorporation of glycerol into phosphatidylglycerol is decreased by the same extent as its incorporation into PC. All of these data suggest that there is a common site(s) at which CCl4 inhibits PC synthesis and that the inhibition occurs early in the biosynthetic pathway. However, individual enzymes involved in phospholipid synthesis do not seem to be affected by the solvent. Exposure of alveolar type II cells to CCl4 does cause a rapid and dramatic loss in cellular ATP, a cofactor required by some enzymes involved in PC synthesis. Studies with isolated lung mitochondria suggest that CCl4 inhibits the enzyme complex which catalyzes the synthesis of ATP from ADP. In addition, CCl4 causes a decrease in the amount of 3-O-methylglucose associated with type II cells, suggesting that glucose influx is impaired. This may also contribute to lower cellular ATP levels. The results of this study suggest that inhalation of CCl4 may impair surfactant phospholipid synthesis by decreasing ATP levels in alveolar type II cells.

Adenosine Triphosphate↗

PubMed1988

Association of chlorphentermine with phospholipids in rat alveolar lavage materials, alveolar macrophages and type II cells.

Administration of chlorphentermine to rats leads to an increase in the phospholipid content of pulmonary surfactant materials and alveolar macrophages. It is known that this drug binds to pure phospholipids and prevents their degradation by phospholipases. Therefore, experiments were carried out to determine if chlorphentermine binds to surfactant phospholipids in vitro and to measure the in vivo association of drug with phospholipids in alveolar lavage materials from rats injected with [14C]chlorphentermine. The presence of chlorphentermine in alveolar macrophages, type II cells and other small pneumocytes (a population of lung cells which does not include alveolar macrophages or type II cells) from treated animals was also assessed. Binding of the drug to surfactant phospholipids, as measured with the fluorescent probe, 1-anilino-8-naphthalene sulfonate, occurs in vitro and does not differ in various subfractions of alveolar lavage materials isolated by differential centrifugation. Following daily administration of chlorphentermine to rats for 3 days, the drug appears to be associated with surfactant phospholipids such that the molar ratio is 1:100 (chlorphentermine/phospholipid). Chlorphentermine is also associated with alveolar macrophages (molar ratio, 1:18) and type II cells (molar ratio, 1:33). Not much drug is associated with the population of other lung cells (molar ratio, 1:333). In alveolar macrophages, approx. 70% of the drug seems to be bound to phospholipid and/or sequestered in subcellular organelles. However, only 20% of the chlorphentermine is bound and/or sequestered in type II cells. The results of these experiments suggest that following chlorphentermine administration, the drug is associated with phospholipids in acellular pulmonary lavage materials, alveolar macrophages and type II cells. This drug-phospholipid interaction may impair phospholipid degradation and lead to a phospholipidosis in surfactant materials and alveolar macrophages.

Animals↗

PubMed1988

The alveolar type II epithelial cell: a multifunctional pneumocyte.

The epithelial surface of the alveoli is composed of alveolar type I and type II cells. Alveolar type I cells comprise 96% of the alveolar surface area. These cells are extremely thin, thus, minimizing diffusion distance between the alveolar air space and pulmonary capillary blood. Type II cells are spherical pneumocytes which comprise only 4% of the alveolar surface area, yet they constitute 60% of alveolar epithelial cells and 10-15% of all lung cells. Four major functions have been attributed to alveolar type II cells: (1) synthesis and secretion of surfactant; (2) xenobiotic metabolism; (3) transepithelial movement of water; and (4) regeneration of the alveolar epithelium following lung injury. Therefore, alveolar type II cells play important roles in normal pulmonary function and in the response of the lung to toxic compounds which may cause lung damage. Techniques have now been developed to isolate and purify alveolar type II epithelial cells from lung tissue. Such cellular preparations afford bioassay systems to monitor the effects of occupational or environmental pollutants on alveolar pneumocytes and should yield important information concerning the etiology of pulmonary disease in the alveolar region of the lung.

Animals↗

PubMed1988

Degradation of pulmonary surfactant disaturated phosphatidylcholines by alveolar macrophages.

Experiments were performed to determine whether rat pulmonary surfactant disaturated phosphatidylcholines (DSPC) are degraded by alveolar macrophages in vitro. When [3H]choline-labeled surfactant materials are incubated with unlabeled alveolar macrophages, approximately 40% of the labeled DSPC is broken down in 6 h. There is just a slight decrease in the specific activity of DSPC, which suggests that most products of degradation are not reincorporated into DSPC, at least during the 6-h incubation period. There is a time- and temperature-dependent association of surfactant DSPC with alveolar macrophages, and some of the cell-associated materials are released from the cell fragments after sonication. Association of surfactant with the cells precedes degradation. The breakdown of surfactant DSPC by intact alveolar macrophages lags behind that produced by sonicated cell preparations with disrupted cell membranes. These data and other information suggest that the surfactant materials are internalized by the cells, before the breakdown. The products of degradation probably include free choline and fatty acids, most of which appear in the extracellular fluid. The breakdown processes do not seem to depend on the physical form of the surfactant or on the presence of surfactant apoproteins. Incubation of the cells alone also results in disappearance of intracellular DSPC, some of which may be surfactant phospholipid taken up by the cells in vivo. These results indicate that alveolar macrophages can degrade surfactant DSPC and suggest that these cells may be involved in catabolism of pulmonary surfactant materials.

1,2-Dipalmitoylphosphatidylcholine↗